BACKGROUND:Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS:293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS:At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS:Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Concerns around the efficacy of 19-20 Gy single dose HDR BT as monotherapy, based on early data, may have been unfounded. Long-term outcome data up to 10 years show no significant difference in PSA control and overall survival compared to 2 and 3 fractions of HDR-BT.

Purpose/objective: Long-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence. Materials/methods: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified. For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence post HDR BT, the recurrent nodules were contoured on the diagnostic T2-weighted MRI and choline PET which were registered to the original HDR BT planning CT. Dosimetric parameters of CTV, planning target volume (PTV), DIL and organs at risk (OARs) were evaluated. Wilcoxon signed-rank test was performed to investigate if there were any significant differences in dosimetric parameters between cases and controls. Cox regression analysis was performed to explore if there were any clinical and dosimetric parameters predicting for biochemical progression free survival (bPFS), local recurrence free survival (LR-PFS) and DIL recurrence free survival (DIL-PFS). Results: Between 2013 and 2018, 180 patients received 19 Gy HDR-BT monotherapy. With a median follow up of 36 months, 19 (10.6%) patients developed biochemical recurrence. Of the 19 patients with biochemical failure, 13 had a local recurrence, including 7 who occurred at the site of DIL. Thirty-eight intermediate/high risk patients were included in the matched pair analysis. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p > 0.05). For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS. Conclusion: No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions. Crown Copyright (C) 2021 Published by Elsevier B.V. All rights reserved.

Purpose: To compare the biochemical control rates (BCRs), late gastrointestinal (GI) and genitourinary (GU) toxicities in patients with low-and intermediate risk prostate cancer (PCa) treated with high dose-rate brachytherapy (HDR BT) of 19 Gy/1 fraction, 26 Gy/2 fractions, or stereotactic ablative radiotherapy (SABR) of 36.25 Gy/5 fractions. Methods and materials: Between August 2008 and December 2017, patients with low-and intermediate risk PCa who received single dose or 2-fraction HDR BT, or 5-fraction SABR at a single institution were included. BCR for the whole population and the individual treatment groups were calculated using the Phoenix definition. Post treatment GI and GU toxicities were evaluated according to the CTCAE v4.0 guidelines. Results: 185 patients with low-and intermediate risk PCa were included in this study with a median follow up of 60.5 months. BCRs at 3 and 5 years were 95% and 85% for all patients. The 5-year BCRs were 69%, 95% and 92% for the 19 Gy/1 fraction, 26 Gy/2 fractions and 36.25 Gy/5 fractions groups respectively. The cumulative 5-year incidence rates of > grade 2 GI events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 0%, 2% and 4%, respectively. Incidence rates in those treated in the 5-fraction SABR arm were significantly higher (p < 0.05) than those treated in both HDR BT arms where no statistically significant difference between the two HDR BT groups was seen (p = 0.15). The cumulative 5-year incidence rates of > grade 2 GU events in the 19 Gy/1fr, 26 Gy/2fr and 36.25 Gy/5fr groups were 30%, 5% and 6%, respectively. No statistically significant difference was found between the 26 Gy/2fr and 36.25 Gy/5fr (p = 0.37) treatment arms but the incidence rate in the 26 Gy/2fr were significantly lower than those seen after 19 Gy/1fr (p < 0.05). Conclusions: 26 Gy/2 fractions HDR BT provided equivalent BCR with lower toxicity compared to 36.25 Gy/5 fractions SABR. Both 2-fraction HBR BT and 5-fraction SABR achieved better BCRs than single dose 19 Gy HDR BT. The two-fraction HDR BT schedule should be considered as an important comparator in future clinical trials. Crown Copyright (c); 2021 Published by Elsevier B.V. All rights reserved. Radiotherapy and Oncology 158 (2021) 184-190

Aim: The dominant intraprostatic lesion (DIL) is the commonest site of relapse after single dose high -dose-rate brachytherapy (HDR-BT) for localised prostate cancer. This study investigated toxicity and clin-ical outcomes of focal dose escalation to the DIL with dose de-escalation to the remaining prostate. Materials/Methods: Between November 2012 and July 2016, 50 patients with localised prostate adenocar-cinoma received single fraction HDR-BT. 21 Gy was prescribed to the DIL, with two de-escalation pre-scription schedules for the remaining prostate. Primary outcomes included biochemical no evidence of disease (bNED), local recurrence free survival (LRFS), and metastasis free survival (MFS). Secondary out-comes included late genitourinary, gastrointestinal and sexual toxicity. Kaplan-Meier analyses with log rank tests were used to estimate bNED, LRFS and MFS. Results: With a median follow up of 70.6 months, 15 patients developed biochemical failure, including 8 in the group that received minor dose de-escalation to the non-DIL prostate (group 1) and 7 in the group that received moderate de-escalation (group 2). Five-year bNED was 88% in group 1 and 76% in group 2 (p = 0.05). Overall 4-year and 5-year FFLF in group 1 was 100% and 96% and in group 2 92% and 84%. These differences were statistically significant (p = 0.03). No acute >G3 genitourinary or >G2 gastrointestinal toxicity was reported. The median IIEF decreased in the first 6 months improving to a peak median score of 20 at 54 months. Conclusion: Focal boost to the DIL did not improve biochemical or local control after single-fraction HDR monotherapy compared to what would be expected from 19 Gy single fraction treatment to the whole gland. Crown Copyright (c) 2021 Published by Elsevier B.V. All rights reserved. Radiotherapy and Oncology 159 (2021) 67-74

Aims: To evaluate focal high dose rate (HDR) brachytherapy in locally recurrent prostate cancer. Materials and methods: Patients with biochemical relapse after non-surgical primary treatment for localised prostate cancer were selected after a negative screen for metastatic disease. Template mapping biopsies combined with multiparametric magnetic resonance imaging were used to identify the location of the tumour and the focal clinical target volume. The planning aim dose prescription was 19 Gy. Outcome measures were biochemical relapse-free survival and toxicity using International Prostate Symptom Score and Common Terminology Criteria for Adverse Events (version 4.0) scores. Results: Between March 2013 and December 2018, 50 patients underwent salvage HDR brachytherapy. The median follow-up was 21 months (range 1-53). Biochemical progression-free survival at 2 and 3 years was 63% and 46%, respectively. On multivariate analysis, only prostate-specific antigen nadir <0.5 ng/ml post-salvage (P = 0.03, hazard ratio 0.04) was associated with biochemical progression-free survival. Relapse was associated with distant metastases in 11/13 patients in whom this was investigated. Late grade 3 genitourinary toxicities were gross haematuria (three patients), severe lower urinary tract symptoms (two patients), erectile dysfunction (one patient) and urethral stricture requiring surgery (four patients). No acute and late grade 4 or 5 genitourinary and no grade 3 or higher gastrointestinal toxicities were recorded. Conclusions: Focal salvage HDR monotherapy achieves biochemical control in 46% of patients at 3 years with acceptable toxicity rates in selected patients. Biochemical relapse was related to a post-salvage prostate-specific antigen nadir of >= 0.5 ng/ml. Long-term outcomes are needed to assess the impact on the natural history of prostate cancer in these patients. (C) 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for >= 2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m(2) 3-weekly x 6 + prednisolone 10mg daily; or SOC + abiraterone acetate 1000mg = prednisolone 5mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) < 1 favours SOC + AAP, and HR>1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting >= 1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naive prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.

The non-parametric Wilcoxon and Spearman tests were used to estimate the relationships.The data were analyzed using SPSS version 22. ResultsThe gross tumor volume (GTV-t) was greater by FDG-PET/CT-simulation but differences were not statistically significant.However, the gross node volume (GTV-n) and the length of the esophageal tumor were greater by FDG-PET/CT-simulation and these differences were statistically significant (Table 1).The analyzed of DSC showed a great similarity of GTV-t: 0.71 (0.13).A very low DSC was observed in GTV-n: 0.08 (0.47).Data are expressed as median and inter-quantile range.Values greater than 0.7 are often regarded as an excellent agreement.Correlations between volume sizes for PET/CT and CT were determined using a correlation coefficient.There was a very high correlation (0.82) between CT and FDG-PET/CT simulation (p=0.002) in the GTV-tumor volumes.However, this correlation was very low (0.58) in the GTVnode (p=0.01) and length of the esophageal tumor (0.67, p=0.001).

Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2.5% one-sided a for hazard ratio (HR) 0.75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0.94, 95% CI 0.79-1.11; p= 0.450), 81 months (41 to not reached) for SOC + Doc (0.78, 0.66-0.93; p= 0.006), and 76 months (39 to not reached) for SOC + ZA + Doc (0.82, 0.69-0.97; p= 0.022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

Patients with locally advanced rectal cancer receive preoperative chemoradiation as the standard of care, producing a pathological complete response in 10–20% and a complete clinical response (CCR) in 20–30%. Small observational studies suggest a selective non-operative management with rigorous surveillance is an option and is increasingly being advocated in many parts of the world for patients who achieve a CCR or near CCR. The assumption is that oncological outcomes for good responders, who are observed, compare favourably with patients subjected to radical surgery. Late regrowth of the primary is rare, almost invariably endoluminal and, hence, can be salvaged. However, concerns remain among some surgeons and oncologists regarding the reproducibility of published results in routine practice. We have previously reviewed this topic. The aim of this brief overview was to re-assess the feasibility and safety of a non-operative approach based on the currently available literature. We make recommendations as to the quality of care required to undertake this management. Significant heterogeneity remains in the initial inclusion criteria, staging and restaging methods, study design, timing of assessment, duration and rigour of follow-up of the trials reviewed — all of which obscure the validity of the results.

The general effectiveness of radiotherapy has improved over time, owing to improvements in technology which have enabled, among others, image-guided and intensity-modulated approaches to be used. In this Perspectives article, the authors describe how these advances can be best implemented for treatment of squamous-cell carcinoma of the anus.